Relative Contraindication For Liver Transplantation Research Articles

Hepatocellular-Cholangiocarcinoma Collision Tumors: An Update of Current Management Practices.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare form of primary hepatic collision tumor, with an incidence ranging from 0.4 to 14.2%. Given the diagnostic challenges and lack of randomized trials, standardized treatment has yet to be established. We aim to review the literature to summarize the diagnosis, molecular characteristics, current treatment modalities, and challenges for cHCC-CC. A literature review was performed using PubMed. We included studies investigating and describing cHCC-CC, focusing on surgical, medical, and radiologic treatments. Overall prognosis is poor, with a 5-year survival rate under 30%. Minor or major hepatectomy with R0 resection is the only curative treatment; however, recurrence is likely (as high as 50% within 5years). The role of liver transplantation is also highly debated given the biliary nature of these tumors, with cHCC-CC as a relative contraindication for liver transplantation. Although gemcitabine-based treatments had higher progression-free survival over sorafenib, there is no standard chemotherapy regimen. Treatment with gemcitabine and platinum demonstrates improved disease control rates compared to gemcitabine in conjunction with 5-fluorouracil (78.4% verse 38.5% respectively). Additionally, platinum-containing chemotherapy regimens exhibit a higher overall response rate than non-platinum regimens (21.4% verse 7.0% respectively). These molecular-directed therapies have prolonged survival for HCC, but further investigation needs to be done to assess their utility in patients with cHCC-CC. cHCC-CC is a rare and complex subset of primary hepatic neoplasms with a dismal prognosis and unstandardized treatment options. Further trials need to be performed to investigate systemic chemotherapy and immunotherapy options for patients with unresectable disease.

Abstract No. 184 Pre-operative portal vein recanalization-transjugular intrahepatic portosystemic shunt for chronic, obliterative portal vein thrombosis: outcomes following liver transplantation

High-grade portal vein thrombosis (PVT) is often considered to be a relative contraindication for liver transplantation (LT). This study compares patients with chronic, obliterative PVT, who underwent portal vein recanalization-transjugular intrahepatic portosystemic shunt (PVR-TIPS) and subsequent LT, to those with partial, non-occlusive PVT who underwent LT without an intervention.

Predictors of do-not-resuscitate order utilization in decompensated cirrhosis hospitalized patients: A nationwide inpatient cohort study

Introduction and objectivesDecompensated cirrhosis carries high inpatient morbidity and mortality. Consequently, advance care planning is an integral aspect of medical care in this patient population. Our study aims to identify do-not-resuscitate (DNR) order utilization and demographic disparities in decompensated cirrhosis patients. Patients or materials and methodsNationwide Inpatient Sample was used to extract the cohort of patients from January 1st, 2016 to December 31st, 2017, based on the most comprehensive and recent data. The first cohort included hospitalized patients with decompensated cirrhosis. The second cohort included patients with decompensated cirrhosis with at least one contraindication for liver transplantation. ResultsA cohort of 585,859 decompensated cirrhosis patients was utilized. DNR orders were present in 14.2% of hospitalized patients. DNR utilization rate among patients with relative contraindication for liver transplantation was 15.0%. After adjusting for co-morbid conditions, disease severity, and inpatient mortality, African-American and Hispanic patient populations had significantly lower DNR utilization rates. There were regional, and hospital-level differences noted. Moreover, advanced age, advanced stage of decompensated cirrhosis, inpatient mortality, and relative contraindications for liver transplantation (metastatic neoplasms, dementia, alcohol misuse, severe cardiopulmonary disease, medical non-adherence) were independently associated with increased DNR utilization rates. ConclusionsThe rate of DNR utilization in patients with relative contraindications for liver transplantation was similar to patients without any relative contraindications. Moreover, there were significant demographic and hospital-level predictors of DNR utilization. This information can guide resource allocation in educating patients and their families regarding prognosis and outcome expectations.

Bariatric surgery before, during, and after liver transplantation: asystematic review and meta-analysis.

Morbid obesity is considered a relative contraindication for liver transplantation (LTX) because of increased risk of complications. The aim of this study was to investigate the role of bariatric surgery before, during, and after LTX. A systematic review of MEDLINE, EMBASE, CENTRAL, and PubMed databases was performed for studies investigating bariatric surgery in patients before, during, or after LTX. Random-effects meta-analysis of proportions was used to calculate pooled effect estimates. One hundred eighty-seven patients underwent bariatric surgery before LTX (8 studies). After surgery, 82% (95% confidence interval, 62%-97%) of patients were successfully listed for LTX and 70% (95% confidence interval, 40%-93%) successfully received LTX. The 30-day mortality rate was 0%. The graft survival rate after 1 year was 70% (95% confidence interval, 30%-99%). Thirty-day minor and major complications rate was 4% and 1%, respectively. Thirty-two patients underwent bariatric surgery during LTX (2 studies). The 30-day mortality rate after surgery was 0% and 1-year graft survival was 100%. Sixty-four patients underwent bariatric surgery after LTX (9 studies). The 30-day mortality was 0%, but 5 deaths occurred beyond 30 days (7.8%). Bariatric surgery may be safe and feasible as a bridge to LTX for patients who would otherwise be ineligible and post-LTX patients for weight loss.

Posttransplant Outcome of Lean Compared With Obese Nonalcoholic Steatohepatitis in the United States: The Obesity Paradox.

Morbid obesity is considered a relative contraindication for liver transplantation (LT). We investigated if body mass index (BMI; lean versus obese) is a risk factor for post-LT graft and overall survival in nonalcoholic steatohepatitis (NASH) and non-NASH patients. Using the United Network for Organ Sharing (UNOS) database, LT recipients from January 2002 to June 2013 (age ≥18years) with follow-up until 2017 were included. The association of BMI categories calculated at LT with graft and overall survival after LT were examined. After adjusting for confounders, all obesity cohorts (overweight and class 1, class 2, and class 3 obesity) among LT recipients for NASH had significantly reduced risk of graft and patient loss at 10years of follow-up compared with the lean BMI cohort. In contrast, the non-NASH group of LT recipients had no increased risk for graft and patient loss for overweight, class 1, and class 2 obesity groups but had significantly increased risk for graft (P<0.001) and patient loss (P=0.005) in the class 3 obesity group. In this retrospective analysis of the UNOS database, adult recipients selected for first LT and NASH patients with the lowest BMI have the worse longterm graft and patient survival as opposed to non-NASH patients where the survival was worse with higher BMI.

Systematic review with meta-analysis: post-operative complications and mortality risk in liver transplant candidates with obesity.

International guidelines rate class III (morbid) obesity (body mass index [BMI]≥40 kg/m2 ) as a relative contraindication for liver transplantation (LT) requiring further research. Moreover, data on the mortality risk in candidates with a BMI: 30-34.9 and 35-39.9 kg/m2 (class I and class II obesity, respectively) are weak. To compare post-operative complications and mortality risks in all obese candidates vs candidates with a BMI: 18.5-29.9 (normal/overweight) assumed as controls. We searched the Cochrane library, PubMed, Scopus, Web-of-Science and article reference lists, restricted to the English language, and selected cohort studies analysing the following outcomes: all-causes mortality (at 30 days, 1-2-3-5 years), post-operative and cardiopulmonary complications, hospital and intensive care unit (ICU) length of stay. Two reviewers independently extracted the studies data and a third one resolved discrepancies. Twenty-four studies comprising 132 162 patients met the inclusion criteria. As compared to controls, mortality risk was increased at all time-periods (except at 3 years) for a BMI≥40, at 30 days for a BMI: 30-34.9 and in none of the considered time-periods for a BMI: 35-39.9. Post-operative complications were significantly higher for a BMI>30 and 30-34.9. Due to the shortage/absence of data, we evaluated cardiopulmonary complications, hospital and ICU length of stay only in the BMI≥30 category. In these patients, only cardiopulmonary complications were increased as compared to controls. Morbid obesity has an impact on patients' survival after LT. However, since even a BMI>30 increases post-transplant complications, new strategies should be included in the LT programme to favour weight loss in all obese candidates.

Living Donor Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Experience of a Single Center.

BACKGROUND Because the outcome of liver transplantation for cholangiocarcinoma is often poor, cholangiocarcinoma is a contraindication for liver transplantation in most centers. Combined hepatocellular carcinoma and cholangiocarcinoma is a rare type of primary hepatic malignancy containing features of hepatocellular carcinoma and cholangiocarcinoma. Diagnosing combined hepatocellular carcinoma and cholangiocarcinoma pre-operatively is difficult. Because of sparse research presentations worldwide, we report our experience with living donor liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma. MATERIAL AND METHODS A total of 710 patients underwent living donor liver transplantation at our institution from April 2006 to June 2014; 377 of them received transplantation because of hepatocellular carcinoma with University of California San Francisco (UCSF) staging criteria fulfilled pre-operatively. Eleven patients (2.92%) were diagnosed with combined hepatocellular carcinoma and cholangiocarcinoma confirmed pathologically from explant livers; we reviewed these cases retrospectively. Long-term survival was compared between patients diagnosed with combined hepatocellular carcinoma and cholangiocarcinoma and patients diagnosed with hepatocellular carcinoma. RESULTS The mean age of the patients in our series was 60.2 years, and the median follow-up period was 23.9 months. Four patients were diagnosed with a recurrence during the follow-up period, including one intra-hepatic and three extra-hepatic recurrences. Four patients died due to tumor recurrence. Except for patients with advanced-stage cancer, disease-free survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma compared with that of patients with hepatocellular carcinoma was 80% versus 97.2% in 1 year, and 46.7% versus 92.5% in 3 years (p<0.001), and overall survival was 90% versus 97.2% in 1 year, and 61.7% versus 95.1% in 3 years (p<0.001). CONCLUSIONS Outcomes of liver transplantation for patients with combined hepatocellular carcinoma and cholangiocarcinoma were worse than those for patients with hepatocellular carcinoma in this study. Combined hepatocellular carcinoma and cholangiocarcinoma are presumed to be a relative contraindication for liver transplantation.

Reversal of severe hepatopulmonary syndrome in chronic hepatic cirrhosis by living donor liver transplantation: Report of two cases

Severe hepatopulmonary syndrome (HPS) is a rare complication of decompensated liver cirrhosis and a relative contraindication for liver transplantation. This report describes the treatment of two cases with severe HPS resulting from chronic liver failure by living donor liver transplantation (LDLT). The clinical data of the two cases were reviewed. The parameters included the intrapulmonary shunt ratio as measured by (99m)Tc pulmonary scintigraphy, perioperative treatment and examination results, and the duration of post-transplant hypoxemia. Liver dysfunction was reversed in both patients 2-3 weeks after LDLT. Both patients experienced slightly increased intrapulmonary shunt ratios in the first postoperative month, followed by substantial decreases at postoperative days 90 and 361. These findings suggest severe HPS can be resolved by LDLT. Pulmonary infection requires proper treatment and may be anticipated during the early postoperative course. The differences in the intrapulmonary shunt ratio between these patients may contribute to the differences in the time required for rehabilitation.

Outcome of liver transplantion in recipients older than 65 years: A single center experience

Advanced age was considered a relative contraindication for liver transplantation (LT) in the past. The percentage of older patients referred for LT assessment has markedly increased in almost all LT centers over the last years. The data regarding the outcome of older patients have been contradictory. Therefore, we aimed to evaluate the long-term survival of LT recipients older than 65 years. Between 1982 and 2008, 106 out of 1011 patients (10.5%), who underwent LT at our institution, were older than 65 years. Almost all of these patients were transplanted after 1995. The mean age was 67.5 (65.0–76.4) years and the majority of patients were male (76%). Regarding underlying liver disease the percentage of non-alcoholic steatohepatitis associated cirrhosis was significantly higher in the older age group (15.9% vs. 5.8%, p<0.01) compared to the younger LT cohort. In contrast, alcoholic liver disease was more common in recipients under 65 years (20.4% vs. 14.1%, p<0.01). Significantly more patients in the older group presented with a concomitant hepatocellular carcinoma (40.6% vs. 23.7%, p<0.01). Both groups did not differ with regard to Child-Pugh classification and mean MELD score. The median follow-up of the older patients was 3.2 compared to 5.7 years of the younger cohort. The actuarial patient survival rates at 1-, 5- and 10-years with 85%, 65% and 56% were slightly lower in the older recipients compared to 87%, 75% and 66% of recipients ≤65 years. The major causes of death in the elderly were sepsis (n=13) in the early postoperative period and de-novo cancer (n=6), HCV/HCC recurrence (each n=5) and cardiovascular complications (n=4) in the late one. The incidence of de-novo cancers and cardiovascular diseases were significantly higher in the older age cohort. The percentage of reLTs did not differ between both groups (7.8% vs. 6.5%). Although overall survival was better for younger patients, this study shows that LT recipients older than 65 years have a favourable outcome after LT with a 5- and 10-year survival of 65% and 56%, indicating that liver transplantation should be considered in patients older than 65 years.

Outcome of acute liver failure in the elderly

Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age > or = 60 years, on outcomes in patients with ALF. One thousand one hundred twenty-six consecutive prospective patients from the US Acute Liver Failure Study Group registry were studied. The median age was 38 years (range, 15-81 years). One thousand sixteen patients (90.2%) were younger than 60 years (group 1), and 499 (49.1%) of these had acetaminophen-induced ALF; this rate of acetaminophen-induced ALF was significantly higher than that in patients > or = 60 years (group 2; n = 110; 23.6% with acetaminophen-induced ALF, P < 0.001). The overall survival rate was 72.7% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 67.9% in group 1 and 48.2% in group 2 for non-acetaminophen patients (P < 0.001). The spontaneous survival rate (ie, survival without liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P = 0.27). Age was not a significant predictor of spontaneous survival in multiple logistic regression analyses. Group 2 patients were listed for liver transplantation significantly less than group 1 patients. Age was listed as a contraindication for transplantation in 5 patients. In conclusion, in contrast to previous studies, we have demonstrated a relatively good spontaneous survival rate for older patients with ALF when it is corrected for etiology. However, overall survival was better for younger non-acetaminophen patients. Fewer older patients were listed for transplantation.

Treatment of extensive subacute portal, mesenteric and ileocolic vein thrombosis with recombinant tissue plasminogen activator

Portal or/and mesenteric vein thrombosis is a rare condition with high mortality in an acute form. Therapy of thrombosis is not well defined, although there are some general guidelines that differ according to disease onset and clinical presentation. In acute thrombosis with bowel infarction, surgical resection with possible thrombolysis is advised. The best therapy for the subacute form is not known and the approach differs between centers. For chronic disease, prolonged anticoagulant therapy is recommended. Thrombolysis is well recognized in the treatment of acute ischemic coronary or cerebral diseases. Success of treatment is better if therapy is introduced within a few hours after symptoms have begun. We describe a 25-year-old patient with the subacute form of extensive portal, mesenteric and ileocolic vein thrombosis in the setting of underlying liver cirrhosis due to autoimmune disease. An aggressive therapeutic approach is advised, especially in patients who will eventually undergo liver transplantation, since portal and/or mesenteric vein thrombosis is relative contraindication for liver transplantation in the majority of transplant centers.

The Utility of TIPS in the Management of Budd-Chiari Syndrome

Budd-Chiari syndrome (BCS) is a rare condition associated with hepatic venous outflow obstruction classically treated with portosystemic shunts or liver transplantation. Recent reports indicate promising results with the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of these patients. We reviewed a 10-year single-institution experience with TIPS in patients diagnosed with BCS. Eleven patients with BCS underwent TIPS procedures, 3 of whom carried a diagnosis of paroxysmal nocturnal hemoglobinuria, a relative contraindication for liver transplantation. One TIPS procedure was unsuccessful for technical reasons. No patient suffered mortality or major morbidity related to the TIPS procedure. The mean reduction of portal venous pressures was 43.7%, with a mean decrease of 73% in the pressure gradient. Of the 7 patients where long-term follow-up was available, 57% had shunts which remained patent but required several nonsurgical revisions for occlusion, with an average assisted patency of 37.5 months. TIPS is an effective modality in the treatment of patients with BCS, especially for those who are not candidates for liver transplantation. TIPS can be successfully used as a bridge to surgical portosystemic shunting, as well as liver transplantation, but may cause technical difficulties when performing transplantation.

HEPATITIS B VIRUS AND LIVER TRANSPLANTATION

Hepatitis B virus (HBV) infection affects more than 300 million persons worldwide and is ranked among the top 10 lethal infectious diseases by the World Health Organization. 45 Liver transplantation is the treatment of choice for patients with liver failure caused by acute or chronic HBV-related liver disease. Early experience with liver transplantation of hepatitis B–infected patients was discouraging. 99 Recurrent HBV infection was common and associated with an aggressive clinical course leading to graft loss and even death within the first few years following transplantation. As a result, HBV infection came to be regarded as a relative contraindication for liver transplantation in many transplant programs, and the proportion of liver transplants performed for HBV-related cirrhosis declined from 5.8% in 1990 to 3.6% in 1993 (Fig. 1) . 102 Therapies, such as hepatitis B immunoglobulin (HBIg), lamivudine , and famciclovir , have significantly improved outcomes by reducing the frequency of recurrent HBV infection and increasing graft and patient survival. 46 , 80 , 96 Consequently, HBV infection is no longer a contraindication for liver transplantation in most transplant programs, and attitudes regarding the treatment options available for HBV-infected patients are optimistic. This article reviews the natural history of HBV infection in liver transplant recipients, and the pathology, pathogenesis, and treatment of post-transplant hepatitis.

Hepatopulmonary syndrome and liver transplantation: a review of the peroperative management of seven paediatric cases.

Until recently, hypoxaemia was considered as a relative contraindication for liver transplantation. The hepatopulmonary syndrome associated with a right to left shunt of blood through the lungs is reversible in adults and children after correction of the cirrhosis by liver transplantation. However, concerns have been raised regarding the risks of anaesthesia in such hypoxaemic patients. Since the peroperative management of children undergoing liver transplantation and suffering from hepatopulmonary syndrome and severe hypoxemia has never been described, we report here our experience in seven children. Despite the fact that severe arterial desaturation was recorded throughout the procedure, no major complications were recorded peroperatively. The postoperative intubation time was 58 +/- 21 h, five children being extubated while still hypoxaemic. All seven patients reversed their hepatopulmonary syndrome after a mean postoperative period of 24 +/- 10 weeks. This shows that liver transplantation can be successfully achieved in severely hypoxaemic children and that postoperative correction of the right to left shunt is then obtained.

Effect of obesity on clinical outcomes in liver transplantation

Severe obesity is often considered a relative contraindication for liver transplantation. The purpose of this study was to evaluate the impact of obesity on clinical measures of liver transplantation outcome. Six hundred eighteen patients underwent liver transplantation between 12/84 and 6/8/92; Body Mass Index (BMI) information was available for 391 patients. When these patients were stratified according to BMI, there were 299 non-obese patients (BMI < 27.8-men, < 27.3-women), 55 obese patients (BMI ≥ 27.8-men, ≥ 27.3-women), and 37 severely obese patients (BMI ≥ 31.1-men, ≥ 32.3-women). The groups were equal by age and sex. Hospital length of stay (LOS), ICU LOS, rates of wound infection, respiratory infection, respiratory failure (need for intubation), rejection, graft and patient survival were evaluated between the groups. Measures of outcome and morbidity were no worse in the obese/severely obese groups than in the non-obese group. An identical result was obtained when patients were classified into two groups (obese vs. non-obese). Wound infection, respiratory infection, and respiratory failure occurred more frequently in the severely obese group but were not significantly higher than the non-obese or obese groups. The hospital LOS tended to be longer in the severely obese patients when compared to the other groups. Chronic obesity alone should not be used as the only criteria to exclude patients from liver transplantation.